1. Field of the Invention
The invention relates to method of use of a combination of the antiandrogen (5.alpha.,17.alpha.)-1'-(methylsulfonyl)-1'H-pregn-20-yno[3,2-c]pyrazol-17 -ol (Win 49596) and the 5.alpha.-reductase inhibitor (5.alpha.,17.beta.)-N-(1,1-dimethylethyl)-3-oxo-4-azaandrost-1-ene-17-carb oxamide (finasteride) for treating prostatic disease in a male mammal and pharmaceutical compositions thereof.
2. Information Disclosure Statement
Christiansen et al. U.S. Pat. No. 4,684,636 issued Aug. 4, 1987 describes antiandrogenic sulfonylsteroidopyrazoles including (5.alpha.,17.alpha.)-1'-(methylsulfonyl)-1'H-pregn-20-yno[3,2-c]pyrazol-17 -ol as the product of EXAMPLE 1 and method of use thereof "for effecting an antiandrogenic response in a mammal" and as being "contemplated to be carried out in the human male in the treatment of benign prostatic hypertrophy" and pharmaceutical compositions thereof. The patent does not describe the combination of any sulfonylsteroidopyrazole thereof with any 5.alpha.-reductase inhibitor. (5.alpha.,17.alpha.)-1'-(methylsulfonyl)-1'H-pregn-20-yno[3,2-c]pyrazol-17 -ol has been described by several publications in the pharmaceutical literature as Win 49596. The generic name zanoterone was recently approved by the United States Adopted Name Council for (5.alpha.,17.alpha.)-1'-(methylsulfonyl)-1'H-pregn-20-yno[3,2-c]pyrazol-17 -ol.
Rassmusson et al. U.S. Pat. No. 4,760,071 issued Jul. 26, 1988 describes "17.beta.-N-monosubstituted carbamoyl-4-aza-5.alpha.-androst-1-en-3-one compounds and the use of such compounds as testosterone-5.alpha.-reductase inhibitors" including as EXAMPLE 1a N-tert-butyl-3-oxo-4-aza-5.alpha.-androst-1-ene-17.beta.-carboxamide and method of use thereof for "treating the hyperandrogenic condition[s] of acne vulgaris, seborrhea, femal[e] hirsutism, and benign prostatic hypertrophy" and pharmaceutical compositions "comprising a pharmaceutical carrier and an effective amount" thereof. The patent does not describe the combination of any 17.beta.-N-monosubstituted carbamoyl-4-aza-5.alpha.-androst-1-en-3-one thereof with any antiandrogen.
USAN and the USP Dictionary of Drug Names (1991, p. 257) describes N-tert-butyl-3-oxo-4-aza-5.alpha.-androst-1-ene-17.beta.-carboxamide by the Chemical Abstracts name (5.alpha.,17.beta.)-N-(1,1-dimethylethyl)-3-oxo-4-azaandrost-1-ene-17-carb oxamide and by the generic name finasteride and "[a]ntineoplastic; inhibitor (5 alpha reductase)" utility thereof.
Labrie et al. (Endocrinology, vol. 128, no. 3, pp. 1673-1675, 1991) describes the combination of the nonsteroidal antiandrogen flutamide with the 5.alpha.-reductase inhibitor 4-MA (17.beta.,N,N-diethylcarbamoyl-4-methyl-4-aza-5.alpha.-androstan-3-one) and states that the inhibitory effects thereof "are additive on prostatic growth and on androgensensitive prostatic binding protein mRNA levels in the rat, thus clearly suggesting that such a combination could provide the basis for a further improvement in the therapy of prostate cancer."
The presently described and claimed invention provides a method of use and pharmaceutical compositions of the combination of Win 49596 and finasteride for reducing the size or inhibiting the growth of the prostate in a male mammal in less time than possible with either drug alone.